1. Field of the Invention
The present invention relates to a process for producing chromans, a process for producing intermediate products useful for the synthesis of chromans, and a novel intermediate product useful for the synthesis of chromans.
The chromans produced in accordance with the present invention, including, for example, 2,5,7,8-tetramethyl-6-acetoxy-2-(4-nitrophenyloxy)methylchroman, are useful as intermediate products for biologically active substances, such as tocopherols, and pharmaceutical agents, such as therapeutic agents of diabetes mellitus, or as intermediate products for polymer materials, such as engineering resins, and, additionally, as stabilizers of organic substances, such as fats and fatty oils and synthetic resins.
2. Discussion of the Background
Conventional processes for producing chromans (a) to (d), described below, are known.
(a) Ring Closing Reaction of an Allyl Phenol
A process for producing chromans by ring closing of an allyl phenol obtained by reacting an allyl halide, an allyl alcohol or a diolefin with a phenol (see "DAIYUKIKAGAKU", Vol. 14, pages 215-217).
According to the conventional process (a), for example, a case wherein sodium phenolate is used as a phenol and 1,1-dimethyl-3-halogenated-1-propene is used as an allyl halide is illustrated as follows: ##STR1## where X represents a halogen atom. (b) React on of o-oxybenzyl Alcohol with an Unsaturated Compound
A process for producing chromans by heating and reacting together o-oxybenzyl alcohol and an unsaturated compound with no solvent at a temperature within a range of 180 to 220.degree. C. (see "DAIYUKIKAGAKU", Vol.14, page 220).
According to conventional process (b), for example, a case wherein 1-propene is used as an unsaturated compound is illustrated as follows: ##STR2## (c) Reaction of the Oxidized Product of o-[1-(alkylthio)alkyl]phenol with an Unsaturated compound.
A process for producing chromans by oxidizing o-[1-(alkylthio)alkyl]phenol with silver oxide under mild conditions, and reacting the resulting oxidized product with a vinyl ether [see Bull. Chem. Soc. Japan, Vol. 63, page 1062 (1990)].
According to the conventional process (c), a case wherein vinyl methyl ether is used as a vinyl ether is illustrated as follows: ##STR3## (d) Reaction of a Phenol, a Formaldehyde and an Unsaturated Compound
A process for producing chromans by heating and reacting a phenol, a formaldehyde and an unsaturated compound in a solvent of a hydrocarbon or a halogenated aromatic compound at a temperature within a range of 160 to 250.degree. C. (see Japanese Patent Application Laid-open 92283/1985).
According to tile conventional process (d), a case wherein a pyrroline based compound is used as an unsaturated compound is illustrated as follows: ##STR4##
However, the aforementioned conventional processes (a) to (d) have the following problems, and, therefore, these processes are not satisfactory for producing chromans.
According to conventional process (a), the desired chroman sometimes cannot be produced, depending on the types of the substituents present on the allyl compound or the diolefin which is reacted with the phenol, and the yield is generally low. According to conventional process (b), it is difficult to synthesize the o-oxybenzyl alcohol as the starting material in a high yield, and, therefore, it is difficult to produce chromans in high yield. According to conventional process (c), it is required to use a specific compound o-[1-(alkylthio)alkyl] phenol as the starting material. To oxidize the phenol, it is also required to use expensive silver oxide at the large amount of an equimolar amount or more, and, therefore, the production cost of the desired chromans is increased, disadvantageously. According to conventional process (d), the yield of chromans is generally as low as 10 to 50%.
An object in the field of chroman synthesis is to provide a process for producing chromans, by using readily available starting materials and inexpensive starting materials, in a high yield in a simple and smooth manner at an industrially high productivity. It is another object in the field of chroman synthesis to provide compounds to be used as intermediates for producing chromans.
The present inventors have made efforts to attain these objects. The inventors have found that chromans can be produced in a simple fashion in high yield, by using a readily available phenol compound, a formaldehyde and an unsaturated compound having a carbon-carbon double bond as starting materials and reacting them in the presence of a secondary amine and an acid (see U.S. Pat. No. 5,495,926).
According to this process, the desired chromans can be produced as follows. In the following reaction formulas, herein, an example is illustrated wherein 4-acetoxy-2,3,5-trimethylphenol is used as the phenol compound; 2-methyl-2-propen-1-ol is used as the unsaturated compound having a carbon-carbon double bond; and dibutylamine is used as the secondary amine; and acetic acid is used as the acid: ##STR5## Compared with the aforementioned conventional processes (a) to (d), the process of the present inventors is excellent in that the desired chromans can be produced industrially in a simple manner at low cost, in a high yield, by using readily available starting materials, particularly in that the chromans can be produced in an extremely high yield, when using a compound having a carbon-carbon double bond and a hydroxyl group within the molecule or a compound having a carbon-carbon double bond and an electron withdrawing group such as ester group and acyl group, which is directly bonded to a carbon atom composing the carbon-carbon double bond thereof.